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Summary Coronavirus disease 2019 (COVID-19) progresses mildly in most of the cases; however, about 5% of the patients develop a severe acute respiratory distress syndrome (ARDS). Of all COVID-19 patients 3% need intensive care treatment, which becomes a great challenge for anesthesiology and intensive care medicine, medically, hygienically and for technical safety requirements. For these reasons, only experienced medical and nursing staff in the smallest grouping possible should be assigned. For these team members, a consistent use of personal protective equipment (PPE) is essential. Due to the immense medical challenges, the following treatment guidelines were developed by the ÖGARI (Österreichische Gesellschaft für Anästhesiologie, Reanimation und Intensivmedizin), FASIM (Federation of Austrian Societies of Intensive Care Medicine) and ÖGIAIN (Österreichische Gesellschaft für Internistische und Allgemeine Intensivmedizin und Notfallmedizin). The recommendations given in this article are to be understood as short snapshots of the moment; all basic guidelines are works in progress and will be regularly updated as evidence levels, new study results and additional experience are gathered.

SummaryThe pandemic from the SARS-CoV‑2 virus is currently challenging healthcare systems all over the world. Maintaining appropriate staffing and resources in healthcare facilities is essential to guarantee a safe working environment for healthcare personnel and safe patient care. Extracorporeal membrane oxygenation (ECMO) represents a valuable therapeutic option in patients with severe heart or lung failure. Although only a limited proportion of COVID-19 patients develop respiratory or circulatory failure that is refractory to conventional treatment, it is of utmost importance to clearly define criteria for the use of ECMO in this steadily growing patient population. The ECMO working group of the Medical University of Vienna has established the following recommendations for ECMO support in COVID-19 patients.

Zusammenfassung Die aktuelle COVID-19-Pandemie, die durch das SARS-CoV‑2 ausgelöst wird, hat bereits in vielen betroffenen Ländern zu gravierenden Ressourcenengpässen der jeweiligen Gesundheitssysteme geführt. Obwohl sehr viele COVID-19-Patienten nur moderate Symptome zeigen, entwickelt eine Subgruppe ein schweres respiratorisches oder auch kardiales Versagen. Die extrakorporale Membranoxygenierung (ECMO) stellt eine wertvolle Therapieoption für Patienten mit therapierefraktärem Lungen- oder Herzversagen dar. Es bedarf klarer Empfehlungen, die den ECMO-Einsatz in dieser zahlenmäßig stetig steigenden Patientenpopulation regeln. Die ECMO-Arbeitsgruppe der Medizinischen Universität Wien hat daher die folgenden Empfehlungen für eine ECMO-Unterstützung bei COVID-19-Patienten formuliert.

Background General anesthesia may cause atelectasis and deterioration in oxygenation in obese patients. The authors hypothesized that individualized positive end-expiratory pressure (PEEP) improves intraoperative oxygenation and ventilation distribution compared to fixed PEEP. Methods This secondary analysis included all obese patients recruited at University Hospital of Leipzig from the multicenter Protective Intraoperative Ventilation with Higher versus Lower Levels of Positive End-Expiratory Pressure in Obese Patients (PROBESE) trial (n = 42) and likewise all obese patients from a local single-center trial (n = 54). Inclusion criteria for both trials were elective laparoscopic abdominal surgery, body mass index greater than or equal to 35 kg/m2, and Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score greater than or equal to 26. Patients were randomized to PEEP of 4 cm H2O (n = 19) or a recruitment maneuver followed by PEEP of 12 cm H2O (n = 21) in the PROBESE study. In the single-center study, they were randomized to PEEP of 5 cm H2O (n = 25) or a recruitment maneuver followed by individualized PEEP (n = 25) determined by electrical impedance tomography. Primary endpoint was Pao2/inspiratory oxygen fraction before extubation and secondary endpoints included intraoperative tidal volume distribution to dependent lung and driving pressure. Results Ninety patients were evaluated in three groups after combining the two lower PEEP groups. Median individualized PEEP was 18 (interquartile range, 16 to 22; range, 10 to 26) cm H2O. Pao2/inspiratory oxygen fraction before extubation was 515 (individual PEEP), 370 (fixed PEEP of 12 cm H2O), and 305 (fixed PEEP of 4 to 5 cm H2O) mmHg (difference to individualized PEEP, 145; 95% CI, 91 to 200; P < 0.001 for fixed PEEP of 12 cm H2O and 210; 95% CI, 164 to 257; P < 0.001 for fixed PEEP of 4 to 5 cm H2O). Intraoperative tidal volume in the dependent lung areas was 43.9% (individualized PEEP), 25.9% (fixed PEEP of 12 cm H2O) and 26.8% (fixed PEEP of 4 to 5 cm H2O) (difference to individualized PEEP: 18.0%; 95% CI, 8.0 to 20.7; P < 0.001 for fixed PEEP of 12 cm H2O and 17.1%; 95% CI, 10.0 to 20.6; P < 0.001 for fixed PEEP of 4 to 5 cm H2O). Mean intraoperative driving pressure was 9.8 cm H2O (individualized PEEP), 14.4 cm H2O (fixed PEEP of 12 cm H2O), and 18.8 cm H2O (fixed PEEP of 4 to 5 cm H2O), P < 0.001. Conclusions This secondary analysis of obese patients undergoing laparoscopic surgery found better oxygenation, lower driving pressures, and redistribution of ventilation toward dependent lung areas measured by electrical impedance tomography using individualized PEEP. The impact on patient outcome remains unclear. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Mechanical ventilation can lead to ventilator-induced lung injury (VILI). In addition to the well-known mechanical forces of volutrauma, barotrauma, and atelectrauma, non-mechanical mechanisms have recently been discussed as contributing to the pathogenesis of VILI. One such mechanism is oscillations in partial pressure of oxygen (PO2) which originate in lung tissue in the presence of within-breath recruitment and derecruitment of alveoli. The purpose of this study was to investigate this mechanism’s possible independent effects on lung tissue and inflammation in a porcine model. Methods To separately study the impact of PO2 oscillations on the lungs, an in vivo model was set up that allowed for generating mixed-venous PO2 oscillations by the use of veno-venous extracorporeal membrane oxygenation (vvECMO) in a state of minimal mechanical stress. While applying the identical minimal-invasive ventilator settings, 16 healthy female piglets (weight 50 ± 4 kg) were either exposed for 6 h to a constant mixed-venous hemoglobin saturation (SmvO2) of 65% (which equals a PmvO2 of 41 Torr) (control group), or an oscillating SmvO2 (intervention group) of 40–90% (which equals PmvO2 oscillations of 30–68 Torr)—while systemic normoxia in both groups was maintained. The primary endpoint of histologic lung damage was assessed by ex vivo histologic lung injury scoring (LIS), the secondary endpoint of pulmonary inflammation by qRT-PCR of lung tissue. Cytokine concentration of plasma was carried out by ELISA. A bioinformatic microarray analysis of lung samples was performed to generate hypotheses about underlying pathomechanisms. Results The LIS showed significantly more severe damage of lung tissue after exposure to PO2 oscillations compared to controls (0.53 [0.51; 0.58] vs. 0.27 [0.23; 0.28]; P = 0.0025). Likewise, a higher expression of TNF-α (P = 0.0127), IL-1β (P = 0.0013), IL-6 (P = 0.0007), and iNOS (P = 0.0013) in lung tissue was determined after exposure to PO2 oscillations. Cytokines in plasma showed a similar trend between the groups, however, without significant differences. Results of the microarray analysis suggest that inflammatory (IL-6) and oxidative stress (NO/ROS) signaling pathways are involved in the pathology linked to PO2 oscillations. Conclusions Artificial mixed-venous PO2 oscillations induced lung damage and pulmonary inflammation in healthy animals during lung protective ventilation. These findings suggest that PO2 oscillations represent an independent mechanism of VILI.

OBJECTIVES Previous studies demonstrated that preconditioning with argon gas provided a marked reduction in inflammation and apoptosis and increased myocardial contractility in the setting of acute myocardial ischaemia-reperfusion (IR). There is substantial evidence that myocardial IR injury following cardioplegic arrest is associated with the enhancement of apoptosis and inflammation, which is considered to play a role in cardiac functional impairment. Therefore, the present study was designed to clarify whether preconditioning with argon gas enhances recovery of cardiac function following cardioplegic arrest. METHODS Sprague-Dawley rats were anaesthetized and ventilated and allocated to (i) the control group (control IR, n = 10) and (ii) the in vivo group (argon IR), which received 3 cycles of argon (50% argon, 21% oxygen and 29% nitrogen, n = 10) administered for 5 min interspersed with 5 min of a gas mixture (79% nitrogen and 21% oxygen). The hearts were excised and then evaluated in an erythrocyte-perfused isolated working heart system. Cold ischaemia (4°C) for 60 min was induced by histidine-tryptophan-ketoglutarate cardioplegia, followed by 40 min of reperfusion. Cardiac functional parameters were assessed. In left ventricular tissue samples, the expressions of extracellular-regulated kinase (ERK1/2), AKT serine/threonine kinase (Akt), jun N-terminal kinase (JNK), endothelial nitric oxide synthase (eNOS) and HMGB1: high-mobility group box 1 (HMGB1) protein were assessed by western blot, and high-energy phosphates were evaluated by high-performance liquid chromatography. RESULTS At the end of reperfusion, the rats preconditioned with argon showed significantly enhanced recovery of cardiac output (101 ± 6% vs 87 ± 11%; P

BACKGROUND Continuous venovenous hemodialysis (CVVHD) may generate microemboli that cross the pulmonary circulation and reach the brain. The aim of the present study was to quantify (load per time interval) and qualify (gaseous vs. solid) cerebral microemboli (CME), detected as high-intensity transient signals, using transcranial Doppler ultrasound. MATERIALS AND METHODS Twenty intensive care unit (ICU group) patients requiring CVVHD were examined. CME were recorded in both middle cerebral arteries for 30 minutes during CVVHD and a CVVHD-free interval. Twenty additional patients, hospitalized for orthopedic surgery, served as a non-ICU control group. Statistical analyses were performed using the Mann-Whitney U test or the Wilcoxon matched-pairs signed-rank test, followed by Bonferroni corrections for multiple comparisons. RESULTS In the non-ICU group, 48 (14.5-169.5) (median [range]) gaseous CME were detected. In the ICU group, the 67.5 (14.5-588.5) gaseous CME detected during the CVVHD-free interval increased 5-fold to 344.5 (59-1019) during CVVHD (P

Cerebral microemboli (ME) are frequently generated during orthopaedic surgery and may impair cerebral integrity. However, the nature of cerebral ME, being either of solid or gaseous origin, is poorly investigated. Our primary aim was to determine both the frequency and nature of cerebral ME in generally anaesthetised patients undergoing major orthopaedic surgery.Fifty patients (hip/knee/shoulder prosthesis, spine surgery) were enrolled. Cerebral ME and cerebral blood flow velocity (CBFV) were determined in both middle cerebral arteries for 15 min preoperatively and postoperatively, using transcranial Doppler ultrasound. Cerebral tissue oxygen index, determined by near-infrared spectroscopy, was further examined. Statistical analysis was carried out using the Wilcoxon matched-pairs signed-ranks test (median (25 th ; 75 th percentile), P 0.05).Overall the frequency of postoperative cerebral ME rose to 600% of preoperative values. Primarily gaseous ME occurred preoperatively and postoperatively [19 (6; 63) vs 116 (24; 373), P 0.001], while the number of solid ME was negligibly small [1 (0; 2) vs 2 (0; 6), P 0.001]. CBFV and cerebral tissue oxygen index remained unaltered bilaterally before and after surgery.Our findings indicate that cerebral ME considerably increase after major orthopaedic surgery under general anaesthesia. The predominant accumulation of gaseous ME and their preoperative occurrence, suggest that the general anaesthesia and individual patient factors may contribute to the embolic load in addition to orthopaedic surgery.. NCT02340416.

Background Epidural-related maternal fever (ERMF) is an adverse effect of epidural analgesia during labor and is associated with perinatal and neonatal morbidity. Local anesthetics have been proposed to trigger ERMF via sterile inflammation. Ropivacaine is currently the most frequently used epidural anesthetic and considered least toxic. This study investigates molecular effects of ropivacaine on human umbilical vein endothelial cells (HUVECs) as model system for endothelial cells and human placental trophoblasts (TBs), compares the effects to the putative anti-inflammatory lidocaine and investigates the partially alleviating impact of the anti-inflammatory corticosteroid dexamethasone. Methods HUVECs and TBs were exposed to ropivacaine (35 μM-7 mM) or lidocaine (21 mM) with or without dexamethasone (1 μM). AnnexinV/propidium iodide staining and lactate dehydrogenase release were used to analyze apoptosis and cytotoxicity. Proinflammatory interleukins-6 (IL-6) and IL-8 as well as prostaglandin E2 (PGE2) were measured by enzyme-linked immunosorbent assay (ELISA), while activation of signaling pathways was detected by Western blotting. Oxidative stress was visualized by live cell imaging and quantification of antioxidant proteins, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, platelet endothelial cell adhesion molecule 1, cyclooxygenase 2, and mitochondrial deoxyribonucleic acid by real-time polymerase chain reaction. Dissipation of the mitochondrial membrane potential was assessed with cytofluorimetric analysis using the J-Aggregate (JC-1 staining [cytofluorimetric analysis using the J-Aggregate]). Results Ropivacaine exposure dose-dependently induced apoptosis and an increased release of IL-6, IL-8, and PGE2 from HUVECs and TBs. Furthermore, caspase-3, nuclear factor-κB, and p38 mitogen-activated protein kinase pathways were activated, while extracellular signal-regulated kinase 1/2 and protein kinase B (Akt) were dephosphorylated. Downregulation of antioxidative proteins induced oxidative stress and upregulation of ICAM1, VCAM1, and PECAM1 possibly facilitate leukocyte transmigration. Mitochondrial effects included increased release of the proinflammatory mitochondrial DNA damage-associated molecular patterns, but no significant dissipation of the mitochondrial membrane potential. Conversely, lidocaine exhibited repression of IL-6 and IL-8 release over all time points, and early downregulation of COX2 and cell adhesion molecules, which was followed by a late overshooting reaction. Dexamethasone reduced especially inflammatory effects, but as an inducer of mitophagy, had negative long-term effects on mitochondrial function. Conclusions This study suggests that ropivacaine causes cellular injury and death in HUVECs and TBs via different signaling pathways. The detrimental effects induced by ropivacaine are only partially blunted by dexamethasone. This observation strengthens the importance of inflammation in ERMF.

Chest imaging in patients with acute respiratory failure plays an important role in diagnosing, monitoring and assessing the underlying disease. The available modalities range from plain chest X-ray to computed tomography, lung ultrasound, electrical impedance tomography and positron emission tomography. Surprisingly, there are presently no clear-cut recommendations for critical care physicians regarding indications for and limitations of these different techniques.The purpose of the present European Respiratory Society (ERS) statement is to provide physicians with a comprehensive clinical review of chest imaging techniques for the assessment of patients with acute respiratory failure, based on the scientific evidence as identified by systematic searches. For each of these imaging techniques, the panel evaluated the following items: possible indications, technical aspects, qualitative and quantitative analysis of lung morphology and the potential interplay with mechanical ventilation. A systematic search of the literature was performed from inception to September 2018. A first search provided 1833 references. After evaluating the full text and discussion among the committee, 135 references were used to prepare the current statement.These chest imaging techniques allow a better assessment and understanding of the pathogenesis and pathophysiology of patients with acute respiratory failure, but have different indications and can provide additional information to each other.

Hyperbaric oxygen therapy (HBOT) has been shown to improve tissue hypoxia, neovascularization and ischemia reperfusion injury and reduce pathologic inflammation in various clinical settings and was proposed to be a game changer in treatment of burns. Improved and faster wound healing as well as a reduction of morbidity and mortality after thermal and concomitant carbon monoxide poisoning are expected. In defiance of the observed benefits for burn wounds and carbon monoxide poisoning in animal models and few randomized controlled trials there is an ongoing controversy regarding its use, indications and cost effectiveness. Furthermore, the use of HBOT, its indications and the evidence behind its efficiency are still widely unknown to most physicians involved in the treatment of burn patients. Therefore, a review of the up to date evidence-based literature was performed with a focus on available data of HBOT in burn care, to elaborate its use in acute thermal injury and carbon monoxide intoxication. Although beneficial effects of HBOT seem very likely insufficient evidence to support or disprove the routine use of HBOT in the treatment of burn care was found. Although difficult to carry out because of the high interindividual variability of burns and chronic wounds, the need for larger high-quality prospective randomized double-blinded controlled multicenter trials are necessary to be able to evaluate useful applications, expense and cost-efficiency of HBOT for burn care.

BACKGROUND Critically ill patients with acute respiratory failure admitted to an intensive care unit are at high risk for cerebral hypoxia. We investigated the impact of continuous positive airway pressure (CPAP) therapy on regional cerebral tissue oxygenation (rSO2). MATERIALS AND METHODS In total, 40 extubated surgical intensive care unit patients requiring classic oxygen therapy (COT) for acute respiratory failure were examined. Near-infrared spectroscopy (INVOS 5100C, Covidien) was used for 30 minutes to detect bilateral rSO2 during COT via facemask (6 L/min) and CPAP therapy (40% fraction of inspired oxygen, 8 cm H2O CPAP) using a randomized crossover study design. Patients served as their own control. Continuous hemodynamic routine monitoring and blood gas analysis were performed. The effect of CPAP therapy on rSO2 and influence of assessed covariables were investigated using a mixed linear model. RESULTS Median rSO2 increased from 57.9% (95% confidence interval [CI], 54.2-61.5) during COT to 62.8% (95% CI, 59.2-66.5) during CPAP therapy (P

Clinical monitoring and recording of vital signs is essential for the therapy and outcome of critically ill patients in the perioperative setting. Most hospital systems are capable of displaying standard clinical parameters and storage of data at low temporal resolution. However, the assessment of novel clinical parameters, e.g. cumulative time of desaturation or hypotension, or the acquisition of highly sampled vital signs is not routinely provided. This limits the possibilities of anesthesiologists and intensivists to proactively tailor patient care and thus limits patient safety. We developed VREACT, a system for real-time assessment of novel clinical parameters and high resolution vital signs recording, which is easy-to-use and applicable in the clinical routine as well as during complex experimental measurements. VREACT was already successfully utilized for one clinical pilot trial and one experimental pig study. We are currently working on the integration of standard and novel clinical parameters into perioperative care.

Background Cyclic recruitment and de-recruitment of atelectasis (c-R/D) is a contributor to ventilator-induced lung injury (VILI). Bedside detection of this dynamic process could improve ventilator management. This study investigated the potential of automated lung sound analysis to detect c-R/D as compared to four-dimensional computed tomography (4DCT). Methods In ten piglets (25 ± 2 kg), acoustic measurements from 34 thoracic piezoelectric sensors (Meditron ASA, Norway) were performed, time synchronized to 4DCT scans, at positive end-expiratory pressures of 0, 5, 10, and 15 cmH2O during mechanical ventilation, before and after induction of c-R/D by surfactant washout. 4DCT was post-processed for within-breath variation in atelectatic volume (Δ atelectasis) as a measure of c-R/D. Sound waveforms were evaluated for: 1) dynamic crackle energy (dCE): filtered crackle sounds (600–700 Hz); 2) fast Fourier transform area (FFT area): spectral content above 500 Hz in frequency and above −70 dB in amplitude in proportion to the total amount of sound above −70 dB amplitude; and 3) dynamic spectral coherence (dSC): variation in acoustical homogeneity over time. Parameters were analyzed for global, nondependent, central, and dependent lung areas. Results In healthy lungs, negligible values of Δ atelectasis, dCE, and FFT area occurred. In lavage lung injury, the novel dCE parameter showed the best correlation to Δ atelectasis in dependent lung areas (R2 = 0.88) where c-R/D took place. dCE was superior to FFT area analysis for each lung region examined. The analysis of dSC could predict the lung regions where c-R/D originated. Conclusions c-R/D is associated with the occurrence of fine crackle sounds as demonstrated by dCE analysis. Standardized computer-assisted analysis of dCE and dSC seems to be a promising method for depicting c-R/D. Electronic supplementary material The online version of this article (10.1186/s13054-018-1964-6) contains supplementary material, which is available to authorized users.

Background Primary graft dysfunction (PGD) after lung transplantation (LTx) carries significant morbidity and mortality in the early post-operative period and is associated with the development of chronic lung allograft dysfunction. AP301, an activator of epithelial sodium channel–mediated Na + uptake represents a new concept for prevention and treatment of pulmonary edema and has shown promising results in the pre-clinical setting. This pilot study investigated the clinical effect of inhaled AP301 on patients with development of PGD > 1 according to International Society of Heart and Lung Transplantation criteria after primary LTx in a high-volume center and was conducted as a randomized, placebo-controlled, single-center pilot-study including 20 patients. All consecutive patients fulfilling inclusion criteria were screened for PGD at arrival on the intensive care unit (ICU) after LTx. After randomization, inhaled AP301 or placebo was administered by nebulizer twice daily for 7 days or until extubation. Otherwise, patients were treated according to routine clinical protocol. Partial pressure of arterial oxygen (Pa o 2 )/fraction of inspired oxygen (F io 2 ) values were obtained until extubation and assessed as a primary outcome parameter. Patients were monitored for 30 days within the study protocol. Results From July 2013 to August 2014, 20 patients were randomized 1:1 to AP301 (Group 1) or placebo (Group 2). Both groups were comparable with regard to sex (40% women/60% men vs 50% women/50% men), mean age (55 ± 13 vs 54 ± 6 years), comorbidities, and diagnosis leading to LTx. The Pa o 2 /F io 2 ratio at the time of inclusion was comparable in both groups, with a mean 235.65 ± 90.78 vs 214.2 ± 95.84 ( p = 0.405), and there was no significant difference in the extravascular lung water index (13.88 ± 5.28 vs 16 ± 6.29 ml/kg, p = 0.476). The primary end point was mean Pa o 2 /F io 2 ratio values between baseline and Day 3. In the AP301 group, only 1 patient was ventilated at Day 4 and no patients were ventilated after Day 4. In the placebo group, 5 patients were ventilated on Day 4 and 2 patients on Days 5, 6, and 7. The mean increase in the Pa o 2 /F io 2 ratio was significantly higher in Group 1 patients, and the mean between baseline and at 72 hours was 365.6 ± 90.4 in Group 1 vs 335.2 ± 42.3 in Group 2 ( p = 0.049). The duration of intubation was shorter in Group 1 than in Group 2 patients (2 ± 0.82 vs 3.7 ± 1.95 days; p = 0.02). ICU stay was 7.5 ± 3.13 days in Group 1 vs 10.8 ± 8.65 days in group 2 ( p = 0.57). Survival at 30 days was 100%. No severe adverse events were recorded. Conclusions This study was designed as a proof-of-concept pilot study. Although it was not powered to achieve statistical significances, the study demonstrated relevant clinical effects of inhaled AP301 on patients with PGD after primary LTx. The improved gas exchange led to a significantly shorter duration of mechanical ventilation and a trend towards a shorter ICU stay. Further investigation of AP301 for treatment of PGD in larger studies is warranted. Trial Registration The trial is registered at https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-000716-21/AT .

Background High-permeability pulmonary edema is a hallmark of acute respiratory distress syndrome (ARDS) and is frequently accompanied by impaired alveolar fluid clearance (AFC). AP301 enhances AFC by activating epithelial sodium channels (ENaCs) on alveolar epithelial cells, and we investigated its effect on extravascular lung water index (EVLWI) in mechanically ventilated patients with ARDS. Methods Forty adult mechanically ventilated patients with ARDS were included in a randomized, double-blind, placebo-controlled trial for proof of concept. Patients were treated with inhaled AP301 (n = 20) or placebo (0.9% NaCl; n = 20) twice daily for 7 days. EVLWI was measured by thermodilution (PiCCO®), and treatment groups were compared using the nonparametric Mann–Whitney U test. Results AP301 inhalation was well tolerated. No differences in mean baseline-adjusted change in EVLWI from screening to day 7 were found between the AP301 and placebo group (p = 0.196). There was no difference in the PaO2/FiO2 ratio, ventilation pressures, Murray lung injury score, or 28-day mortality between the treatment groups. An exploratory subgroup analysis according to severity of illness showed reductions in EVLWI (p = 0.04) and ventilation pressures (p

BACKGROUND Mechanical ventilation with oxygen is life-saving, however, may result in hyperoxia. The aim was to analyse the incidence and duration of hyperoxia burden and related in-hospital mortality in critically ill patients. METHODS Patients of all ages admitted to intensive care units (ICUs) and with mechanical ventilation for at least seven consecutive days were included in this single centre retrospective medical record audit. The main outcome measure was time-weighted arterial partial pressure of oxygen (PaO2 ) over 7 days. Logistic regression for association with in-hospital mortality and propensity score matching was performed. RESULTS In total, 20,889 arterial blood gases of 419 patients were analysed. Time-weighted mean PaO2 was 14.0 ± 2.4 kPa. Time-weighted mean FiO2 was 49.2 ± 12.1%. Seventy-six (18.1%) patients showed continuous hyperoxia exposure, defined as time-weighted mean PaO2 > 16 kPa. Duration of hyperoxia, hypoxia (PaO2 < 8 kPa) and normoxia (PaO2 8-16 kPa) were 37.9 ± 31.0 h (23.7%), 4.9 ± 9.5 h (3.1%), and 116.8 ± 29.6 h (73.2%). Hyperoxia occurred especially at low to moderate FiO2 in patients of first and second age quartiles (1-57 years) with smaller SAPS2 score. In-hospital mortality of patients with hyperoxia (32.9%) or normoxia did not differ (35.9%; P = 0.691). Conditional logistic regression showed no association between hyperoxia and in-hospital mortality (OR 1.46; 95%CI 0.72-2.96; P = 0.29). CONCLUSION Substantial hyperoxia burden was observed in ICU patients. Young patients with less comorbidities showed hyperoxic episodes more often, especially with lower FiO2 . Hyperoxia during 7 days of mechanical ventilation did not correlate to increased in-hospital mortality.

BACKGROUND Perioperative oxygen (O2) therapy can cause hyperoxia. Extreme hyperoxia can injure the cardiovascular system and remote organs. OBJECTIVE Our primary objective was to test the hypothesis that exposure to moderate hyperoxia will induce injury to human umbilical vein endothelial cells (HUVECs), a model for studying the vascular endothelium under controlled conditions. DESIGN In-vitro cell culture study. SETTING Department of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Austria. Study period from the beginning of October 2013 to the end of July 2014. CELLS HUVECs were isolated from fresh umbilical cords. INTERVENTIONS HUVECs were exposed to constant hyperoxia (40% O2), cyclic hyperoxia/anoxia (40%/0% O2, average 20% O2), constant normoxia (21% O2) and constant anoxia (0% O2) using a cell culture bioreactor. MAIN OUTCOME MEASURES Cell growth, viability and release of IL-6, IL-8 and macrophage migration inhibitory factor were assessed at baseline and after 6, 12, 24 and 48 h of treatment. A phosphokinase array was performed after 60 min of treatment to identify activated cellular signalling pathways. RESULTS Constant hyperoxia and cyclic hyperoxia/anoxia impeded cell growth, reduced viability, triggered a proinflammatory response, proven by IL-6, IL-8 and migration inhibitory factor release, and induced apoptosis and necrosis. The inflammatory and cytotoxicity responses were highest in the constant hyperoxia group. Phosphokinase arrays revealed that different O2 concentrations activated distinct sets of cytoprotective and cell death-associated kinases, including mitogen-activated protein kinases, Src kinases, p53, Akt, mitogen-activated and stress-activated kinase, Lyn, Lck, p70S6, signal transducers and activators of transcription 5b and 6, glycogen synthase kinase 3a/b and 5' AMP-activated protein kinases 1/2. CONCLUSION Continuous moderate hyperoxia and cyclic moderate hyperoxia/anoxia-induced endothelial inflammation, apoptosis and necrosis. Given the large surface area of the vascular endothelium, moderately elevated O2 levels may contribute to cardiovascular inflammation and injury. TRIAL REGISTRATION This in-vitro study was not registered in a database.

Background During cardiopulmonary resuscitation (CPR) the ventilation/perfusion distribution (VA/Q) within the lung is difficult to assess. This experimental study examines the capability of multiple inert gas elimination (MIGET) to determine VA/Q under CPR conditions in a pig model. Methods Twenty-one anaesthetised pigs were randomised to three fractions of inspired oxygen (1.0, 0.7 or 0.21). VA/Q by micropore membrane inlet mass spectrometry-derived MIGET was determined at baseline and during CPR following induction of ventricular fibrillation. Haemodynamics, blood gases, ventilation distribution by electrical impedance tomography and return of spontaneous circulation were assessed. Intergroup differences were analysed by non-parametric testing. Results MIGET measurements were feasible in all animals with an excellent correlation of measured and predicted arterial oxygen partial pressure (R2 = 0.96, n = 21 for baseline; R2 = 0.82, n = 21 for CPR). CPR induces a significant shift from normal VA/Q ratios to the high VA/Q range. Electrical impedance tomography indicates a dorsal to ventral shift of the ventilation distribution. Diverging pulmonary shunt fractions induced by the three inspired oxygen levels considerably increased during CPR and were traceable by MIGET, while 100% oxygen most negatively influenced the VA/Q. Return of spontaneous circulation were achieved in 52% of the animals. Conclusions VA/Q assessment by MIGET is feasible during CPR and provides a novel tool for experimental purposes. Changes in VA/Q caused by different oxygen fractions are traceable during CPR. Beyond pulmonary perfusion deficits, these data imply an influence of the inspired oxygen level on VA/Q. Higher oxygen levels significantly increase shunt fractions and impair the normal VA/Q ratio.

BACKGROUND Cyclic alveolar recruitment and derecruitment play a role in the pathomechanism of acute lung injury and may lead to arterial partial pressure of oxygen (PaO(2) ) oscillations within the respiratory cycle. It remains unknown, however, if these PaO(2) oscillations are transmitted to the microcirculation. The present study investigates if PaO(2) oscillations can be detected in the pig buccal mucosa microcirculation. METHODS Respiratory failure was induced by surfactant depletion in seven pigs. PaO(2) oscillations caused by cyclic recruitment and derecruitment were measured in the thoracic aorta by fast fluorescence quenching of oxygen technology. Haemoglobin oxygen saturation, haemoglobin amount and blood flow in the buccal mucosa microcirculation were determined by combined fast white light spectrometry and laser Doppler flowmetry additionally to systolic arterial pressure. Measurements were performed during baseline conditions and during cyclic recruitment and derecruitment. RESULTS Measurements remained stable during baseline. Respiratory-dependent oscillations occurred in the systemic circulation [PaO(2) oscillations 92 (69-172) mmHg; systolic arterial pressure oscillations 33 (13-35) %] and were related to the respiratory rate (5.0 ± 0.2/min) as confirmed by Fourier analysis. Synchronised oscillations were detected to the pig buccal mucosa microcirculation [haemoglobin oxygen saturation oscillations 3.4 (2.7-4.9) %; haemoglobin amount oscillations 8.5 (2.3-13.3) %; blood flow oscillations 66 (18-87) %]. The delay between PaO(2) -\ and microcirculatory oxygen oscillations was 7.2 ± 2.8 s. CONCLUSION The present study suggests that PaO(2) oscillations caused by cyclic recruitment and derecruitment were transmitted to the buccal mucosa microcirculation. This non-invasive approach of measuring oxygen waves as a surrogate parameter of cyclic recruitment and derecruitment could be used to monitor PaO(2) oscillations at the bedside.

Electrical impedance tomography (EIT) is considered useful for monitoring regional ventilation and aeration in intensive-care patients during mechanical ventilation. Changes in their body fluid state modify the electrical properties of lung tissue and may interfere with the EIT measurements of lung aeration. The aim of our study was to assess the effects of crystalloid and colloid infusion and blood withdrawal on bioimpedance determined by EIT in a chest crosssection. Fourteen anaesthetized mechanically ventilated pigs were subjected to interventions affecting the volume state (crystalloid and colloid infusion, blood withdrawal). Six animals received additional crystalloid fluids (fluid group) whereas eight did not (no-fluid group). Global and regional relative impedance changes (RIC, dimensionless unit) were determined by backprojection at endexpiration. Regional ventilation distribution was analyzed by calculating the tidal RIC in the same regions. Colloid infusion led to a significant fall in the global end-expiratory RIC (mean differences: fluid: −91.2, p < 0.001, nofluid: −38.9, p < 0.001), which was partially reversed after blood withdrawal (mean differences, fluid: +45.1, p = 0.047 and no-fluid: +26.2, p = 0.009). The RIC was significantly lower in the animals with additional crystalloids (mean group difference: 45.5, p < 0.001). Global and regional tidal volumes were not significantly affected by the fluid and volume states.

The forced oscillation technique (FOT) allows the measurement of respiratory mechanics in the intensive care setting. The aim of this study was to compare the FOT with a reference method during mechanical ventilation through a tracheal tube. The respiratory impedance spectra were measured by FOT in nine anaesthetized pigs, and resistance and compliance were estimated on the basis of a linear resistance-compliance inertance model. In comparison, resistance and compliance were quantified by the multiple linear regression analysis (LSF) of conventional ventilator waveforms to the equation of motion. The resistance of the sample was found to range from 6 to 21 cmH(2)O s l(-1) and the compliance from 12 to 32 ml cmH(2)O(-1). A Bland-Altman analysis of the resistance resulted in a sufficient agreement (bias -0.4 cmH(2)O s l(-1); standard deviation of differences 1.4 cmH(2)O s l(-1); correlation coefficient 0.93) and test-retest reliability (coefficient of variation of repeated measurements: FOT 2.1%; LSF 1.9%). The compliance, however, was poor in agreement (bias -8 ml cmH(2)O(-1), standard deviation of differences 7 ml cmH(2)O(-1), correlation coefficient 0.74) and repeatability (coefficient of variation: FOT 23%; LSF 1.7%). In conclusion, FOT provides an alternative for monitoring resistance, but not compliance, in tracheally intubated and ventilated subjects.

Background: The pathophysiological concept of acute lung injury (ALI) in combination with ventilator-associated lung injury (VALI) is still unclear. We characterized the histopathological features of intravenous injection of oleic acid (OAI) and lung lavage (LAV) combined with VALI. Methods: Pigs were randomized to the control, LAV or OAI group and ventilated by pressure-controlled ventilation. Measurements included: haemodynamics, spirometry, blood gas analysis, lung wet-to-dry weight ratio (W/D), total protein content in broncho-alveolar lavage fluid (BALF), and lung pathological description and scoring. Results: Five hours after lung injury induction, gas exchange was significantly impaired in both the OAI and the LAV groups. Compared to controls, we found an increase in W/D and histopathological total injury scores in both the LAV and OAI groups and an increase in BALF total protein content in the OAI group. In contrast to the LAV group, the OAI group showed septal necrosis and alveolar oedema. Both groups exhibited dorsal and caudal atelectasis and interstitial oedema. In addition, the OAI group demonstrated a propensity to dorsal necrosis and congestion whereas the LAV group tended to develop ventral overdistension and barotrauma. Conclusions: This study presents a comparison of porcine OAI and LAV models combined with VALI, providing information for study design in research on ALI.

BACKGROUND: In the acute respiratory distress syndrome potentially recruitable lung volume is currently discussed. (3)He-magnetic resonance imaging ((3)He-MRI) offers the possibility to visualize alveolar recruitment directly. METHODS: With the approval of the state animal care committee, unilateral lung damage was induced in seven anesthetized pigs by saline lavage of the right lungs. The left lung served as an intraindividual control (healthy lung). Unilateral lung damage was confirmed by conventional proton MRI and spiral-CT scanning. The total aerated lung volume was determined both at a positive end-expiratory pressure (PEEP) of 0 and 10 mbar from three-dimensionally reconstructed (3)He images, both for healthy and damaged lungs. The fractional increase of aerated volume in damaged and healthy lungs, followed by a PEEP increase from 0 to 10 mbar, was compared. RESULTS: Aerated gas space was visualized with a high spatial resolution in the three-dimensionally reconstructed (3)He-MR images, and aeration defects in the lavaged lung matched the regional distribution of atelectasis in proton MRI. After recruitment and PEEP increase, the aerated volume increased significantly both in healthy lungs from 415 ml [270-445] (median [min-max]) to 481 ml [347-523] and in lavaged lungs from 264 ml [71-424] to 424 ml [129-520]. The fractional increase in lavaged lungs was significantly larger than that in healthy lungs (healthy: 17% [11-38] vs. lavage: 42% [14-90] (P=0.031). CONCLUSION: The (3)He-MRI signal might offer an experimental approach to discriminate atelectatic vs. poor aerated lung areas in a lung damage animal model. Our results confirm the presence of potential recruitable lung volume by either alveolar collapse or alveolar flooding, in accordance with previous reports by computed tomography.

Various supportive and adjunctive therapies to conventional mechanical ventilation have been evaluated in patients with acute lung injury and acute respiratory distress syndrome (e.g. nitric oxide, prone position, surfactant, glucocorticoids). Although some investigations have shown promising improvements in oxygenation and physiological variables, large randomized trials of adjunctive and supportive therapies showed no impact on survival.

Intermittent hypoxia may occur in a number of clinical scenarios, including interruption of myocardial blood flow or breathing disorders such as obstructive sleep apnea. Although intermittent hypoxia has been linked to cardiovascular and cerebrovascular disease, the effect of intermittent hypoxia on the human heart is not fully understood. Therefore, in the present study, we compared the cellular responses of cultured human adult cardiac myocytes (HACMs) exposed to intermittent hypoxia and different conditions of continuous hypoxia and normoxia.HACMs were exposed to intermittent hypoxia (0%-21% O2), constant mild hypoxia (10% O2), constant severe hypoxia (0% O2), or constant normoxia (21% O2), using a novel cell culture bioreactor with gas-permeable membranes. Cell proliferation, lactate dehydrogenase release, vascular endothelial growth factor release, and cytokine (interleukin [IL] and macrophage migration inhibitory factor) release were assessed at baseline and after 8, 24, and 72 hours of exposure. A signal transduction pathway finder array was performed to determine the changes in gene expression.In comparison with constant normoxia and constant mild hypoxia, intermittent hypoxia induced earlier and greater inflammatory response and extent of cell injury as evidenced by lower cell numbers and higher lactate dehydrogenase, vascular endothelial growth factor, and proinflammatory cytokine (IL-1β, IL-6, IL-8, and macrophage migration inhibitory factor) release. Constant severe hypoxia showed more detrimental effects on HACMs at later time points. Pathway analysis demonstrated that intermittent hypoxia primarily altered gene expression in oxidative stress, Wnt, Notch, and hypoxia pathways.Intermittent and constant severe hypoxia, but not constant mild hypoxia or normoxia, induced inflammation and cell injury in HACMs. Cell injury occurred earliest and was greatest after intermittent hypoxia exposure. Our in vitro findings suggest that intermittent hypoxia exposure may produce rapid and substantial damage to the human heart.

Background: PGD following LuTX carries significant morbidity and mortality. AP301, an activator of ENaC-mediated Na(+) uptake represents a new concept for treatment of hyper-permeability oedema with promising preclinical results. Aims: This study aims to investigate the effect of AP301 on patients with PGD≥1 at ICU arrival after LuTX. Methods: Prospective randomised, placebo-controlled pilot-study. All patients fulfilling inclusion criteria are screened for PGD at ICU arrival. After randomization AP301 or placebo is administered via nebulizer twice daily for 7 days or until extubation. Otherwise patients are treated according to clinical routine protocol and followed for 30 days within the study. Results: From 7/2013-8/2014 20 patients were randomised 1:1 to AP301 (group 1) or placebo (group 2). Demographics were comparable in both groups as well as mean PaO2/FiO2 ratio at time of inclusion (236±91 vs 214±96). Patients in group 1 had a significantly shorter duration of intubation with 2±0,8 vs 3,7±2 days (p=0,02). There was a trend towards a shorter ICU stay (7,5±3,1 vs 10,8±8,7 days) and increased PaO2/FiO2 ratio in group 1 at 24h (313±126 vs 240±90), 48h (486±59 vs 460±33), 72h (504±40 vs 427±78) and 96h postoperative (549±0 vs 370±96). Thereafter no patient in group 1 was ventilated. 30-day survival was 100%. Conclusion: This pilot study showed impressive clinical effects of AP301 on patients with PGD after primary LuTX leading to a significantly shorter intubation time and a trend towards improved gas exchange and shorter ICU stay. Further investigation of AP301 for PGD treatment is warranted.

BACKGROUND Little is known about real-time in-vivo microscopy of pulmonary capillary perfusion because current microscopy requires direct access to lung tissue with surgical intervention such as the thoracic-window technique and open-lung model. OBJECTIVES To evaluate if probe-based confocal laser scanning endomicroscopy (pCLE) via the trachea allows for real-time in-vivo visualisation of pulmonary capillary density and red blood cell (RBC) velocity in pigs. DESIGN An interventional animal study. SETTING European University Hospital. ANIMALS Nine female domestic pigs (50 to 60 kg) were used. MAIN OUTCOME MEASURES A pCLE probe was positioned in non-dependent, central and dependent lung zones in nine anaesthetised pigs (Alveoflex, Cellvizio, Maunakea, France). After intravenous administration of fluorescein isothiocyanate dextran as contrast agent repetitive pCLE videos were recorded during pressure-controlled ventilation (PCV) or continuous positive airway pressure for 3 min each. Using fluorescein isothiocyanate-labelled RBC erythrocyte velocities in pulmonary capillaries were quantified. Data are expressed as mean ± SD or median with interquartile range (IQR). RESULTS Capillary density was greater in dependent and central as compared with non-dependent lung zones [[32 (29 to 34) %] and 32 (30 to 34) % vs. 28 (26 to 28) %, respectively, P 20 μm, 309 μm s(-1) (209 to 397)] than intermediate [diameter 10.1 to 20 μm, 146 μm s(-1) (118 to 235)] and small [diameter

OBJECTIVE Cyclic recruitment and derecruitment of atelectasis can occur during mechanical ventilation, especially in injured lungs. Experimentally, cyclic recruitment and derecruitment can be quantified by respiration-dependent changes in PaO2 (ΔPaO2), reflecting the varying intrapulmonary shunt fraction within the respiratory cycle. This study investigated the effect of inspiration to expiration ratio upon ΔPaO2 and Horowitz index. DESIGN Prospective randomized study. SETTING Laboratory investigation. SUBJECTS Piglets, average weight 30 ± 2 kg. INTERVENTIONS At respiratory rate 6 breaths/min, end-inspiratory pressure (Pendinsp) 40 cm H2O, positive end-expiratory pressure 5 cm H2O, and FIO2 1.0, measurements were performed at randomly set inspiration to expiration ratios during baseline healthy and mild surfactant depletion injury. Lung damage was titrated by repetitive surfactant washout to induce maximal cyclic recruitment and derecruitment as measured by multifrequency phase fluorimetry. Regional ventilation distribution was evaluated by electrical impedance tomography. Step changes in airway pressure from 5 to 40 cm H2O and vice versa were performed after lavage to calculate PO2-based recruitment and derecruitment time constants (TAU). MEASUREMENTS AND MAIN RESULTS In baseline healthy, cyclic recruitment and derecruitment could not be provoked, whereas in model acute respiratory distress syndrome, the highest ΔPaO2 were routinely detected at an inspiration to expiration ratio of 1:4 (range, 52-277 torr [6.9-36.9 kPa]). Shorter expiration time reduced cyclic recruitment and derecruitment significantly (158 ± 85 torr [21.1 ± 11.3 kPa] [inspiration to expiration ratio, 1:4]; 25 ± 12 torr [3.3 ± 1.6 kPa] [inspiration to expiration ratio, 4:1]; p < 0.0001), whereas the PaO2/FIO2 ratio increased (267 ± 50 [inspiration to expiration ratio, 1:4]; 424 ± 53 [inspiration to expiration ratio, 4:1]; p < 0.0001). Correspondingly, regional ventilation redistributed toward dependent lung regions (p < 0.0001). Recruitment was much faster (TAU: fast 1.6 s [78%]; slow 9.2 s) than derecruitment (TAU: fast 3.1 s [87%]; slow 17.7 s) (p = 0.0078). CONCLUSIONS Inverse ratio ventilation minimizes cyclic recruitment and derecruitment of atelectasis in an experimental model of surfactant-depleted pigs. Time constants for recruitment and derecruitment, and regional ventilation distribution, reflect these findings and highlight the time dependency of cyclic recruitment and derecruitment.

BACKGROUND: Current practice at high-frequency oscillatory ventilation (HFOV) initiation is a stepwise increase of the constant applied airway pressure to achieve lung recruitment. We hypothesized that HFOV would lead to more adverse cerebral haemodynamics than does pressure controlled ventilation (PCV) in the presence of experimental intracranial hypertension (IH) and acute lung injury (ALI) in pigs with similar mean airway pressure settings. METHODS: In 12 anesthetized pigs (24-27 kg) with IH and ALI, mean airway pressure (P(mean)) was increased (to 20, 25, 30 cm H(2)O every 30 min), either with HFOV or with PCV. The order of the two ventilatory modes (cross-over) was randomized. Mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), cerebral blood flow (CBF) (fluorescent microspheres), cerebral metabolism, transpulmonary pressures (P(T)), and blood gases were determined at each P(mean) setting. Our end-points of interest related to the cerebral circulation were ICP, CPP and CBF. RESULTS: CBF and cerebral metabolism were unaffected but there were no differences between the values for HFOV and PCV. ICP increased slightly (HFOV median +1 mm Hg, P

In a surfactant-depletion model of lung injury, tidal recruitment of atelectasis and changes in shunt fraction lead to large Pao2 oscillations. We investigated the effect of these oscillations on conventional arterial blood gas (ABG) results using different sampling techniques in ventilated rabbits. In each rabbit, 5 different ventilator settings were studied, 2 before saline lavage injury and 3 after lavage injury. Ventilator settings were altered according to 5 different goals for the amplitude and mean value of brachiocephalic Pao2 oscillations, as guided by a fast responding intraarterial probe. ABG collection was timed to obtain the sample at the peak or trough of the Pao2 oscillations, or over several respiratory cycles. Before lung injury, oscillations were small and sample timing did not influence Pao2. After saline lavage, when Po2 fluctuations measured by the indwelling arterial Po2 probe confirmed tidal recruitment, Pao2 by ABG was significantly higher at peak (295 +/- 130 mm Hg) compared with trough (74 +/- 15 mm Hg) or mean (125 +/- 75 mm Hg). In early, mild lung injury after saline lavage, Pao2 can vary markedly during the respiratory cycle. When atelectasis is recruited with each breath, interpretation of changes in shunt fraction, based on conventional ABG analysis, should account for potentially large respiratory variations in arterial Po2.

Rasche Anderungen der Lungenbeluftung und -durchblutung, wie zum Beispiel beim Rekrutieren von Atelektasen im Acute Respiratory Distress Syndrome (ARDS) oder wahrend der kardiopulmonalen Reanimation, lassen starke Schwankungen des Sauerstoffpartialdrucks (pO2) im arteriellen Blut erwarten. Ein schneller pO2-Messsensor (Foxy-AL 300™) mit einer zeitlichen Auflosung von bis zu 80 ms ermoglicht eine Online-Messung dieser pO2-Schwankungen und stellt im Tierexperimenten erstmals in Aussicht, diese Veranderungen unmittelbar zu quantifizieren und therapeutischen Interventionen zuzuordnen.

Ziel: Dynamische CT-Untersuchungen (dCT) erlauben die Darstellung und Quantifizierung ventilierter Lungenflache und Atelektasenbildung wahrend kontinuierlicher Beatmung. Diese Studie ­vergleicht eine quantitative Auswertung einer infrakarinalen dCT-Einzelschicht mit der einer Spiral-CT der gesamten Lunge, um zu untersuchen, ob eine dynamisch gemessene Einzelschicht bezuglich der intrapulmonalen Atelektasenverteilung reprasentativ fur die Gesamtlunge ist. Material und Methoden: An 8 gesunden Schweinen erfolgte eine dCT (Schichtdicke 1 mm, zeitliches Inkrement 100 ms) wahrend kontinuierlicher Beatmung, gefolgt von einer Spiral-CT der gesamten Lunge (Schichtdicke 2 mm; Pitch 1,5; Inkrement 2 mm) wahrend inspiratorischen Atemanhalts (Atemwegsdruck 20 mbar). Nach Segmentierung und Dichteplanimetrie der Datensatze mittels einer dafur entwickelten Auswertesoftware wurde eine Differenzierung des Lungengewebes in folgende funktionelle Lungenkompartimente vorgenommen: uberblahte Lunge (- 1024 bis - 910 HE); normoventiliert (- 910 bis - 300 HE); Atelektasen (- 300 bis + 200 HE). Ergebnisse: Die gemittelten Anteile der Dichtebereiche in den dCT-Serien korrelierten mit der Dichteanalyse der Spiral-CT wie folgt: uberblahte Lungenanteile r = 0,56; normoventiliert r = 0,83; Atelektasen r = 0,84. Die Spiral-CT-Auswertung zeigte folgende prozentuale Aufteilung der Lungenkompartimente: uberblaht 3,1 %; normoventiliert 77,9 %; Atelektasen 19,0 %. Die dCT ergab folgende Verteilung der Gesamtlungenflache: uberblahte Lungenflache 6,4 %; normoventiliert 65,2 %; Atelektasen 28,4 %. Schlussfolgerungen: Die Ergebnisse dieser Studie lassen schlussfolgern, dass die Auswirkungen unterschiedlicher Beatmungsstrategien auf die Atelektasenbildung mittels dCT erfasst werden konnen. Hierbei ist jedoch zu beachten, dass es aufgrund eines kraniokaudalen Gradienten der Atelektasenverteilung zu einer systematischen Abweichung zwischen dCT und Spiral-CT kommt. Die uberblahten und atelektatischen Lungenanteile werden in der infrakarinalen Untersuchungsschicht mittels dCT uberschatzt, die normoventilierten Areale unterschatzt. Purpose: Dynamic CT (dCT) allows visualization and quantification of ventilated lung and atelectases with high temporal resolution during continuous ventilation. This study compares a quantitative image analysis in a subcarinal single slice dCT series versus a whole lung spiral-CT, in order to analyze, whether the distribution of atelectasis of a single dCT series is representative for the whole lung. Materials and Methods: dCT in sliding windows technique (slice thickness 1 mm, temporal increment 100 ms) was performed in 8 healthy pigs 3 cm caudal to the ca­rina during continuous mechanical ventilation. Subsequently, a spiral-CT of the whole lung (slice thickness 2 mm; pitch 1.5; increment 2 mm) was acquired during inspiratory breath hold (airway pressure 20 mbar). Lung segmentation and planimetry of predefined density ranges were achieved using a dedicated software tool in both data-sets. Thus, the fractions of the following functional lung compartments were averaged over time: hyperinflated lung (- 1024 to - 910 HE), normal ventilated lung - 900 to - 300 HE) and atelectasis (- 300 to + 200 HE). Results: Quantitative analysis of dCT-series during continuous respiration correlated with the density analysis in spiral-CT as follows: hyperinflated lung r = 0.56; normal ventilated lung r = 0.83 and atelectases r = 0.84. Analysis of spiral-CT showed the following distribution of functional lung compartments: hyperinflated lung 3.1 % normal ventilated lung 77.9 % and atelectasis 19.0 %. In dCT, hyperinflated lung represented 6.4 %, normal ventilated lung 65.2 % and atelectasis 28.4 % of total the lung area. Conclusion: The results of our study demonstrate that dCT allows monitoring of atelectasis formation in response to different ventilatory strat­egies. However, a deviation between dCT and spiral-CT has to be taken into account. In subcarinal dCT series, hyperinflated lung areas and atelectases were overestimated due to a craniocaudal gradient of atelectases, whereas normal ventilated lung was underestimated.

Background Fast dynamic computed tomography (dCT) has been used to assess regional dynamics of lung inflation and deflation processes. The aim of this study was to relate ventilation-induced changes in lung density distribution, as measured over several respiratory cycles by dCT, to oxygenation and shunt fraction in a lavage acute respiratory distress syndrome model. Methods Six anaesthetized pigs underwent pressure-constant ventilation (F I O2=1.0, inspiratory:expiratory ratio=1:1) before and after induction of lung damage by saline lavage. Mean airway pressure ( P a μ w μ ) was varied (8, 13, 18, 23, 28, 33, and 38 cm H2O) in random order. At each P a μ w μ level, dCT acquisitions were performed over several respiratory cycles (Somatom Plus4, Siemens; supradiaphragmatic transverse slice; thickness=1 mm; temporal resolution=100 ms). During scanning at each P a μ w μ , arterial and mixed venous blood were obtained for blood gas analysis and shunt calculation. In each CT image, fractional areas (FA) of defined density ranges representing ventilated lung and atelectasis were determined by planimetry using dedicated software. The FA data of individual 100 ms scans were averaged over several respiratory cycles, and expressed as mean FA in percentage of total lung area at each P a μ w μ . For atelectatic lung parenchyma a quantitative relationship of the respective mean FA to shunt fraction was studied using regression analysis. Results Under steady-state conditions, mean FA of atelectasis correlated linearly with the calculated shunt fraction (healthy lungs, r=+0.76; lavaged lungs, r=+0.89). There is a non-linear relationship between mean FA of ventilated lung parenchyma and mean FA of atelectasis with PaO2. Conclusions We conclude that dCT allows assessment of the effects of ventilator adjustments and resultant P a μ w μ ; changes upon lung aeration and oxygenation rapidly, and with good spatial and temporal resolution. This may benefit patients with acute lung injury, whose ventilatory pattern may be optimized as early as during their first diagnostic workup.

This study examined whether ARDS patients in whom predefined ventilator settings fail to maintain oxygenation and CO2 removal can be safely transitioned to high-frequency oscillatory ventilation (HFOV), and whether HFOV use is efficacious.Prospective observational study in the 14-bed intensive care unit of a university hospital.42 patients with ARDS (APACHE II score 28 (IQR 24-37) and ventilation time prior HFOV 3.0 days (0.7-9.1).Gas exchange parameters and ventilator data were recorded before and during HFOV treatment (-12 h, -6 h, baseline, 10 min, 1 h, 6 h, 12 h, 24 h). Primary endpoints included: (a) PaO2/FIO2 ratio 24 h after start of HFOV treatment or the last point of measurement if HFOV ended within the first 24 h; (b) HFOV-related complications. Post hoc analysis assessed the relationship between outcome and the response to HFOV, and between outcome and time of mechanical ventilation prior to HFOV. At baseline the median PaO2/FIO2 ratio was 95 (IQR 62-129); after 24 h of HFOV the PaO2/FIO2 ratio had increased significantly to 165 (88-225); only one patient developed a unilateral pneumothorax. Of the 42 patients 18 (43%) had died by day 30. Subset analyses showed a significantly higher 30-day mortality rate in patients with at least 3 days of mechanical ventilation prior to HFOV (64%) and in patients without oxygenation improvement after 24 h on HFOV (71%).HFOV is an effective and safe method to ventilate ARDS patients. Failure to improve oxygenation within 24 h of HFOV is associated with high mortality.

Background: To use 3Helium (3He)-MRI in patients with unilateral lung grafts to assess the contributions of graft and native lung to total ventilated lung volume, and second to compare conventional measurements of intrapulmonary gas volume (spirometry, body plethysmography) with image-based volumetry of ventilated lung parenchyma visualized by hyperpolarized 3He-MRI. Methods: With Ethics Committee approval, five patients with single lung transplantation (SLTX) for idiopathic pulmonary fibrosis (IPF) underwent both conventional pulmonary function testing (PFT) and 3He-MRI of the lung. Intrapulmonary gas volume (GV) during the inspiratory breathhold for 3He-MRI was calculated from measured functional residual capacity (corrected for supine position) and inspired tidal volume. Image-based global and regional lung volumetries (LV) were performed in three-dimensionally reconstructed 3He-MR images (corrected for the fraction of tissue and blood). Results: Transplanted lungs were characterized by a homogeneous distribution of signal intensity, whereas the native lungs of the patients suffering from IPF displayed an inhomogeneous signal distribution pattern with numerous round or wedge-shaped ventilation defects. Total ventilated lung volume determined by 3He-MRI correlated well with PFT-based measurements, but with a systematic overestimation of the 3He-based lung volumetry of approximately 20%. Functioning lung grafts contributed 66±6% and their corresponding native IPF lungs 34±6% to total ventilated volume (P

Objective: To develop an image based technique to study the effect of different ventilatory strategies on lung ventilation and alveolar recruitment during cardiopulmonary resuscitation (CPR). Design: (1) Technical development of the following components: (a) construction of an external chest compression device, which does not interfere with CT imaging, and (b) development of a software tool to detect lung parenchyma automatically and to calculate radiological density parameters. (2) Feasibility studies: three strategies of CPR ventilation were performed and imaged in one animal each (pigs, 25 kg): volume-constant ventilation (VCV), no ventilation, or continuous airway pressure (CPAP). One minute after induction of circulatory arrest inside the CT scanner, external chest compressions started at a rate of 100 cpm, and one of the ventilation modes was initiated. After 1 min, intravenous epinephrine was added as a bolus (40 μg/kg), followed by a continuous infusion (13 μg/kg per min). Six minutes later, dynamic CT acquisitions (temporal resolution: 100 ms) commenced. Simultaneously, arterial blood gases, acid base status and haemodynamics were sampled. Results: Using a modified chest compression device, dynamic CT acquisitions are feasible during closed-chest CPR. In three pilot experiments with different ventilation strategies, the dedicated software tool allowed to quantify ventilated, atelectatic and over-distended fractions of total lung area. VCV showed a large amount of atelectasis, which was recruited during every respiratory cycle. No ventilation led to atelectasis to govern over 50% of the total lung area. CPAP caused less atelectasis as VCV, and no cyclic recruitment and de-recruitment phenomena were observed. Conclusions: We demonstrate a novel experimental set up, which allows quantification of different lung compartments during ongoing CPR and may become useful in comparing the direct pulmonary effects of different ventilatory strategies in the settings of Basic and Advanced Cardiac Life Support.

The inhaled route is a promising new way for administering drugs to the human body. Flow and particle deposition in the human respiratory tract depends on the individual's anatomy as well as on the drug composition. A European Framework V Program supported project is currently developing a simulation tool for assessment of drug distribution and deposition. This tool relies heavily on the input of radiological data sets, which are obtained in humans. Both high temporal and spatial resolutions are required, and CT and MRI (including hyperpolarized helium-3 MRI) are applied. The radiological data are integrated into computation fluid dynamics software, which is capable of assessing air-flow profiles and compartmental behaviours. This is complemented by pharmacokinetic models, which should result in a simulation tool that will be of use for the theoretical design of new inhaled therapies. This article describes the special imaging requirements of each region of the respiratory tract and the feasibility of these sophisticated radiological techniques with a view of using these data in a simulation model of the lung.

PURPOSE Determination of the intrahepatic distribution volume of two contrast media (CM) by CT-guided application in an ex-vivo and an in-vivo model (pig liver). MATERIAL AND METHODS In pig livers ex-vivo and in-vivo, 131 CT-guided injections of two different CM (Imagopaque(R), Visipaque(R)) were performed using catheters and cannula with and without side-holes and documented by spiral CT. The distribution pattern was assessed visually: interstitial, subcapsular, vascular/tubular, the distribution volume was quantified using a density mask (thresholds 70/400 HE). RESULTS Purely interstitial applications were achieved more frequently in-vivo than ex-vivo (p = 0.001). There were no relevant differences between the two CM. Catheters without side-holes led to more interstitial CM depots than catheters with side-holes (p = 0.005). The mean distribution volume was larger with catheters with side-holes (ex-vivo 103 cm(3), in-vivo 19 cm(3)) than with catheters without side-holes (ex-vivo 67 cm(3), in-vivo 13 cm(3)) (p = 0,01). At the same time, the mean density with catheters with side-holes (102 HE) was lower than with catheters without side-holes (115 HE) (p = 0.005). CONCLUSION Marked differences of the CM distribution volumes were observed between ex-vivo and in-vivo studies in the pig model. Catheters with side-holes are far superior to catheters without.

Computed tomography (CT) is the method of choice for the morphological assessment of pulmonary structure. Airways. pulmonary parenchyma and their pathologies are shown with high spatial resolution. Airway diseases exhibit bronchial dilatation, wall thickening and an increased visibility in the lung periphery. CT is also the imaging gold standard for the detection and the characterisation of emphysema because a high degree of concordance with histopathological studies. Centrilobular, panlobular and paraseptal emphysema can be differentiated. CT can also provide functional information. Paired inspiratory and expiratory scans with or without spirometric triggering allow to evaluate obstruction of the small airways (airtrapping). On the basis of CT-data lung volumes can be semented. Cine-CT allows to visualise motion of the central airways. e.g. in tracheomalacia, to assess regional ventilation to calculate pulmonary time constants. and to display the co-ordinated or dissociated motion of the thoracic wall and the diaphragm. Beyond the mere high-resolution visualisation of the structure of the lung the application of these CT-strategies makes a regional assessment of pulmonary function possible.

BackgroundTechnically assisted assessment of volume status before surgery may be useful to direct intraoperative fluid administration. We therefore tested a recently developed whole-body bioimpedance spectroscopy device to determine pre- to postoperative fluid distribution.MethodsUsing a three-compartment physiologic tissue model, the body composition monitor (BCM, Fresenius Medical Care, Germany) measures total body fluid volume, extracellular volume, intracellular volume and fluid overload as surplus or deficit of 'normal' extracellular volume. BCM-measurements were performed before and after standardized general anaesthesia for gynaecological procedures (laparotomies, laparoscopies and vaginal surgeries). BCM results were blinded to the attending anaesthesiologist and data analysed using the 2-sided, paired Student's t-test and multiple linear regression.ResultsIn 71 females aged 45 ± 15 years with body weight 67 ± 13 kg and Duration of anesthesia 154 ± 69 minutes [corrected] duration of anaesthesia 154 ± 68 min, pre- to postoperative fluid overload increased from -0.7 ± 1.1 L to 0.1 ± 1.0 L, corresponding to -5.1 ± 7.5% and 0.8 ± 6.7% of normal extracellular volume, respectively (both pConclusionsRoutine intraoperative fluid administration results in a significant, and clinically meaningful increase in the extracellular compartment. BCM-measurements yielded plausible results and may become useful to guide intraoperative fluid therapy in future studies.

Purpose of the Study: Detection of cyclical recruitment of atelectasis after induction of lavage (LAV) or oleic acid injury (OAI) in mechanically ventilated pigs. Primary hypothesis is that oxygen oscillations within the respiratory cycle can be detected by SpO2 recordings (direct hint). SpO2 oscillations reflect shunt oscillations that can only be explained by cyclical recruitment of atelectasis. Secondary hypothesis is that electrical impedance tomography (EIT) depicts specific regional changes of lung aeration and of pulmonary mechanical properties (indirect hint). Materials and Methods: Three groups (each n = 7) of mechanically ventilated pigs were investigated applying above mentioned methods before and repeatedly after induction of lung injury: (1) sham treated animals (SHAM), (2) LAV, and (3) OAI. Results: Early oxygen oscillations occurred in the LAV group (mean calculated amplitude: 73.8 mmHg reflecting shunt oscillation of 11.2% in mean). In the OAI group oxygen oscillations occurred hou...

A method for in vivo measurement of oxygen partial pressure (pO2) in porcine lungs during partial liquid ventilation (PLV) with perflubron (PFOB) was developed. A pulse sequence for high-resolution MRI of the distribution of PFOB in the lung after intratracheal administration was developed as well. Moreover, quantitative measurements of longitudinal relaxation time T(1) of (19)F resonances for assessment of regional pO2 are described. Due to the need to acquire data during a single expiratory breathhold, only low SNRs were achieved in vivo. Therefore, simulations were performed to investigate the influence of background noise on T(1) values calculated from data with low SNR. Based on these simulations, a postprocessing strategy was developed to correct for systematic errors by background noise prior to quantitative analysis. Results of a pilot study in pigs under conditions of PLV are presented.

Purpose: Density measurements in dynamic CT image series of the lungs allow one to quantify ventilated, hyperinflated, and atelectatic pulmonary compartments with high temporal resolution. Fast automatic segmentation of lung parenchyma and a subsequent evaluation of it's respective density values are a prerequisite for any clinical application of this technique. Material and Methods: For automatic lung segmentation in thoracic CT scans, an algorithm was developed which uses (a) different density masks, and (b) anatomic knowledge to differentiate heart, diaphragm and chest wall from ventilated and atelectatic lung parenchyma. With Animal Care Committee approval, the automated technique was tested in 8 anaesthetized ventilated pigs undergoing dynamic CT before and after induction of lavage-ARDS. Images were acquired in one supradiaphragmatic, cross-sectional slice (temporal resolution of 100 ms; slice thickness of 1 mm, high resolution reconstruction algorithm). In 120 CT images the total pixel number and the calculated MLD from the automatically segmentated lung were compared to the values obtained from an interactive lung segmentation. Results: The software tool was able to read all image series (DICOM standard). Automatic and interactive segmentation were in high agreement (R 2 =0.99 for the total number of pixels and the MLD). Originally, the most frequent error was misclassification of atelectasis as extrapulmonary solid tissue. Conclusion: An automatic software tool is presented for lung segmentation in healthy lungs and in ARDS. Aerated lung and atelectasis were identified with high accuracy. This post-processing tool allows for a quantitative, CT based assessment of ventilation and recruitment processes in the lung. Thus, it may help to optimize ventilation patterns in patients with ARDS.

A new method for dynamic imaging of pulmonary wash-in and wash-out kinetics of inhaled sulfur hexafluoride (SF6) gas was developed. Measurements at the fluorine-19 Larmor frequency were performed in pigs using a gradient echo pulse sequence with 0.5 ms echo time and a measurement time of 9.1 s per image. Dynamic MRI was performed during wash-in and wash-out of SF6 gas in mechanically ventilated porcine lungs. A postprocessing strategy was developed for quantitative determination of wash-out time constants in the presence of noise. Mean wash-out constants were 4.78 ± 0.48 breaths vs. 4.33 ± 0.76 breaths for left and right lung when ventilation was performed with low tidal volume, and 1.73 ± 0.16 breaths vs. 1.85 ± 0.11 breaths with high tidal volume ventilation. In conclusion, breath-hold MRI of SF6 gas is feasible in large animals. Moreover, regional wash-in and wash-out kinetics of SF6 can be determined noninvasively with this new method. Potential human applications are discussed. Magn Reson Med 45:605–613, 2001. © 2001 Wiley-Liss, Inc.